Surveillance of antenatal influenza vaccination: validity of current systems and recommendations for improvement

Abstract Background: Although influenza vaccination is recommended during pregnancy as standard of care, limited surveillance data are available for monitoring uptake. Our aim was to evaluate the validity of existing surveillance in Western Australia for measuring antenatal influenza immunisations. Methods: The self-reported vaccination status of 563 women who delivered between April and October 2013 was compared against three passive data collection sources: a state-wide antenatal influenza vaccination database maintained by the Department of Health, a public maternity hospital database, and a private health service database. Sensitivity, specificity, and positive and negative predictive values were calculated for each system using self-report as the “gold standard.” Results: The state-wide antenatal vaccination database detected 45.7 % (95 % CI: 40.1–51.4 %) of influenza vaccinations, the public maternity hospital database detected 66.7 % (95 % CI: 55.1–76.9 %), and the private health service database detected 29.1 % (95 % CI: 20.5–39.4 %). Specificity exceeded 90 % and positive predictive values exceeded 80 % for each system. Sensitivity was lowest for women whose antenatal care was provided by a private obstetrician. Conclusions: Existing resources for surveillance of antenatal influenza vaccinations detect 29–67 % of vaccinations. Considering the importance of influenza immunisation as a public health intervention, particularly in pregnant women, improvements to routine monitoring of influenza vaccination is warranted

Does Gender Influence Colour Choice in the Treatment of Visual Stress?

Purpose Visual Stress (VS) is a condition in which words appear blurred, in motion, or otherwise distorted when reading. Some people diagnosed with VS find that viewing black text on white paper through coloured overlays or precision tinted lenses (PTLs) reduces symptoms attributed to VS. The aim of the present study is to determine whether the choice of colour of overlays or PTLs is influenced by a patient’s gender. Methods Records of all patients attending a VS assessment in two optometry practices between 2009 and 2014 were reviewed retrospectively. Patients who reported a significant and consistent reduction in symptoms with either overlay and or PTL were included in the analysis. Overlays and PTLs were categorized as stereotypical male, female or neutral colours based on gender preferences as described in the literature. Chi-square analysis was carried out to determine whether gender (across all ages or within age groups) was associated with overlay or PTL colour choice. Results 279 patients (133 males and 146 females, mean age 17 years) consistently showed a reduction in symptoms with an overlay and were included. Chi-square analysis revealed no significant association between the colour of overlay chosen and male or female gender (Chi-square 0.788, p = 0.674). 244 patients (120 males and 124 females, mean age 24.5 years) consistently showed a reduction in symptoms with PTLs and were included. Chi-square analysis revealed a significant association between stereotypical male/female/neutral colours of PTLs chosen and male/female gender (Chi-square 6.46, p = 0.040). More males preferred stereotypical male colour PTLs including blue and green while more females preferred stereotypical female colour PTLs including pink and purple. Conclusions For some VS patients, the choice of PTL colour is influenced not only by the alleviation of symptoms but also by other non-visual factors such as gender

'Not to Be Harsh but Try Less to Relate to 'the Teens' and You'll Relate to Them More': Co-Designing Obesity Prevention Text Messages with Adolescents.

Text messages remain a preferred way for adolescents to communicate, and recent evidence suggests adolescents would like access to digital healthcare options. However, there is limited evidence for text messages to engage adolescent populations in obesity prevention behaviors. We aimed to co-design a bank of text messages that are evidence-based, acceptable, and engaging for adolescents. An established iterative mixed methods process, consisting of three phases, was used to develop the text message program. The first bank of 145 text messages was drafted based on current evidence, behavior change techniques, and input from researchers and health professionals. A survey was then administered to adolescents and professionals for review of text message content, usefulness, understanding, and age-appropriateness. An adolescent research assistant collaborated with the research team on all three phases. Forty participants (25 adolescents and 15 professionals) reviewed the initial bank of 145 text messages. On average, all reviewers agreed the text messages were easy to understand (13.6/15) and useful (13.1/15). In total, 107 text messages were included in the final text message bank to support behavior change and prevent obesity. This study may guide other researchers or health professionals who are seeking to engage adolescents in the co-design of health promotion or intervention content. Effectiveness of the text message program will be tested in a randomized controlled trial

Portuguese propolis disturbs glycolytic metabolism of human colorectal cancer in vitro

Propolis is a resin collected by bees from plant buds and exudates, which is further processed through the activity of bee enzymes. Propolis has been shown to possess many biological and pharmacological properties, such as antimicrobial, antioxidant, immunostimulant and antitumor activities. Due to this bioactivity profile, this resin can become an alternative, economic and safe source of natural bioactive compounds.Antitumor action has been reported in vitro and in vivo for propolis extracts or its isolated compounds; however, Portuguese propolis has been little explored. The aim of this work was to evaluate the in vitro antitumor activity of Portuguese propolis on the human colon carcinoma cell line HCT-15, assessing the effect of different fractions (hexane, chloroform and ethanol residual) of a propolis ethanol extract on cell viability, proliferation, metabolism and death. METHODS: Propolis from Angra do Heroísmo (Azores) was extracted with ethanol and sequentially fractionated in solvents with increasing polarity, n-hexane and chloroform. To assess cell viability, cell proliferation and cell death, Sulforhodamine B, BrDU incorporation assay and Anexin V/Propidium iodide were used, respectively. Glycolytic metabolism was estimated using specific kits. RESULTS: All propolis samples exhibited a cytotoxic effect against tumor cells, in a dose- and time-dependent way. Chloroform fraction, the most enriched in phenolic compounds, appears to be the most active, both in terms of inhibition of viability and cell death. Data also show that this cytotoxicity involves disturbance in tumor cell glycolytic metabolism, seen by a decrease in glucose consumption and lactate production. CONCLUSION: Our results show that Portuguese propolis from Angra do Heroísmo (Azores) can be a potential therapeutic agent against human colorectal cancer.We thank the Portuguese Science and Technology Foundation (FCT) for VMG fellowship (ref. SFRH/BI/33503/2008). The authors thank Mr. Antonio Marques from Frutercoop - Azores, who kindly collected and provided the propolis sample for the study

Geographic variation in the aetiology, epidemiology and microbiology of bronchiectasis

Bronchiectasis is a disease associated with chronic progressive and irreversible dilatation of the bronchi and is characterised by chronic infection and associated inflammation. The prevalence of bronchiectasis is age-related and there is some geographical variation in incidence, prevalence and clinical features. Most bronchiectasis is reported to be idiopathic however post-infectious aetiologies dominate across Asia especially secondary to tuberculosis. Most focus to date has been on the study of airway bacteria, both as colonisers and causes of exacerbations. Modern molecular technologies including next generation sequencing (NGS) have become invaluable tools to identify microorganisms directly from sputum and which are difficult to culture using traditional agar based methods. These have provided important insight into our understanding of emerging pathogens in the airways of people with bronchiectasis and the geographical differences that occur. The contribution of the lung microbiome, its ethnic variation, and subsequent roles in disease progression and response to therapy across geographic regions warrant further investigation. This review summarises the known geographical differences in the aetiology, epidemiology and microbiology of bronchiectasis. Further, we highlight the opportunities offered by emerging molecular technologies such as -omics to further dissect out important ethnic differences in the prognosis and management of bronchiectasis.NMRC (Natl Medical Research Council, S’pore)MOH (Min. of Health, S’pore)Published versio

Protein misfolding and dysregulated protein homeostasis in autoinflammatory diseases and beyond.

Cells have a number of mechanisms to maintain protein homeostasis, including proteasome-mediated degradation of ubiquitinated proteins and autophagy, a regulated process of ‘self-eating’ where the contents of entire organelles can be recycled for other uses. The unfolded protein response prevents protein overload in the secretory pathway. In the past decade, it has become clear that these fundamental cellular processes also help contain inflammation though degrading pro-inflammatory protein complexes such as the NLRP3 inflammasome. Signaling pathways such as the UPR can also be co-opted by toll-like receptor and mitochondrial reactive oxygen species signaling to induce inflammatory responses. Mutations that alter key inflammatory proteins, such as NLRP3 or TNFR1, can overcome normal protein homeostasis mechanisms, resulting in autoinflammatory diseases. Conversely, Mendelian defects in the proteasome cause protein accumulation, which can trigger interferon-dependent autoinflammatory disease. In non-Mendelian inflammatory diseases, polymorphisms in genes affecting the UPR or autophagy pathways can contribute to disease, and in diseases not formerly considered inflammatory such as neurodegenerative conditions and type 2 diabetes, there is increasing evidence that cell intrinsic or environmental alterations in protein homeostasis may contribute to pathogenesis

The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes

Organisms have evolved to survive rigorous environments and are not prepared to thrive in a world of caloric excess and sedentary behavior. A realization that physical exercise (or lack of it) plays a pivotal role in both the pathogenesis and therapy of type 2 diabetes mellitus (t2DM) has led to the provocative concept of therapeutic exercise mimetics. A decade ago, we attempted to simulate the beneficial effects of exercise by treating t2DM patients with 3 weeks of daily hyperthermia, induced by hot tub immersion. The short-term intervention had remarkable success, with a 1 % drop in HbA1, a trend toward weight loss, and improvement in diabetic neuropathic symptoms. An explanation for the beneficial effects of exercise and hyperthermia centers upon their ability to induce the cellular stress response (the heat shock response) and restore cellular homeostasis. Impaired stress response precedes major metabolic defects associated with t2DM and may be a near seminal event in the pathogenesis of the disease, tipping the balance from health into disease. Heat shock protein inducers share metabolic pathways associated with exercise with activation of AMPK, PGC1-a, and sirtuins. Diabetic therapies that induce the stress response, whether via heat, bioactive compounds, or genetic manipulation, improve or prevent all of the morbidities and comorbidities associated with the disease. The agents reduce insulin resistance, inflammatory cytokines, visceral adiposity, and body weight while increasing mitochondrial activity, normalizing membrane structure and lipid composition, and preserving organ function. Therapies restoring the stress response can re-tip the balance from disease into health and address the multifaceted defects associated with the disease

Human aging is characterized by focused changes in gene expression and deregulation of alternative splicing

This is the final version. Available on open access from Wiley via the DOI in this recordSummary: Aging is a major risk factor for chronic disease in the human population, but there are little human data on gene expression alterations that accompany the process. We examined human peripheral blood leukocyte in-vivo RNA in a large-scale transcriptomic microarray study (subjects aged 30-104years). We tested associations between probe expression intensity and advancing age (adjusting for confounding factors), initially in a discovery set (n=458), following-up findings in a replication set (n=240). We confirmed expression of key results by real-time PCR. Of 16571 expressed probes, only 295 (2%) were robustly associated with age. Just six probes were required for a highly efficient model for distinguishing between young and old (area under the curve in replication set; 95%). The focused nature of age-related gene expression may therefore provide potential biomarkers of aging. Similarly, only 7 of 1065 biological or metabolic pathways were age-associated, in gene set enrichment analysis, notably including the processing of messenger RNAs (mRNAs); [P<0.002, false discovery rate (FDR) q<0.05]. This is supported by our observation of age-associated disruption to the balance of alternatively expressed isoforms for selected genes, suggesting that modification of mRNA processing may be a feature of human aging. © 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.National Institute for Health Research (NIHR

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

A UMLS-based spell checker for natural language processing in vaccine safety

BACKGROUND: The Institute of Medicine has identified patient safety as a key goal for health care in the United States. Detecting vaccine adverse events is an important public health activity that contributes to patient safety. Reports about adverse events following immunization (AEFI) from surveillance systems contain free-text components that can be analyzed using natural language processing. To extract Unified Medical Language System (UMLS) concepts from free text and classify AEFI reports based on concepts they contain, we first needed to clean the text by expanding abbreviations and shortcuts and correcting spelling errors. Our objective in this paper was to create a UMLS-based spelling error correction tool as a first step in the natural language processing (NLP) pipeline for AEFI reports. METHODS: We developed spell checking algorithms using open source tools. We used de-identified AEFI surveillance reports to create free-text data sets for analysis. After expansion of abbreviated clinical terms and shortcuts, we performed spelling correction in four steps: (1) error detection, (2) word list generation, (3) word list disambiguation and (4) error correction. We then measured the performance of the resulting spell checker by comparing it to manual correction. RESULTS: We used 12,056 words to train the spell checker and tested its performance on 8,131 words. During testing, sensitivity, specificity, and positive predictive value (PPV) for the spell checker were 74% (95% CI: 74–75), 100% (95% CI: 100–100), and 47% (95% CI: 46%–48%), respectively. CONCLUSION: We created a prototype spell checker that can be used to process AEFI reports. We used the UMLS Specialist Lexicon as the primary source of dictionary terms and the WordNet lexicon as a secondary source. We used the UMLS as a domain-specific source of dictionary terms to compare potentially misspelled words in the corpus. The prototype sensitivity was comparable to currently available tools, but the specificity was much superior. The slow processing speed may be improved by trimming it down to the most useful component algorithms. Other investigators may find the methods we developed useful for cleaning text using lexicons specific to their area of interest